NCT05373108

Endothelin-1 and Cardiac Allograft Vasculopathy (CAV)

Impact of Endothelin-1 on the Development of Cardiac Allograft Vasculopathy in Heart Transplant Recipients: Endothelin Receptor Antagonism and Vasomotor Function

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 19 (actual)
• Sponsor: University of California, Los Angeles · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Many patients with end-stage heart failure, a condition in which the heart fails to pump enough blood to support the body's other organs, are fortunate enough to receive a heart transplant. However, despite taking medicines aimed at blunting the immune system's response to the donor heart, some of them will develop transplant-related disease in the coronary arteries supplying their hearts. Fifty years after the first human-to-human heart transplant, this disorder-cardiac allograft vasculopathy (CAV)-remains a leading cause of long-term death and has been coined the 'Achilles' Heel' of heart transplantation. Indeed, a better understanding of how CAV occurs and improved therapies to prevent and/or slow its development are desperately needed to meaningfully impact patient outcomes. Endothelin-1 (ET-1) is a key molecular regulator of arterial health, and our prior data suggests that it is associated with accelerated CAV. In this particular study of recent heart transplant recipients, we are asking: Does ET-1 contribute to the coronary artery's capacity to dilate/constrict? To answer this question, during the cardiac catheterization at 1 year post-transplant (standard of care), we will measure blood levels of ET-1 and perform an invasive evaluation of coronary vasomotor function inn a consecutive subset of patients who will have received a 1-week course of the oral endothelin receptor antagonist (macitentan) prior this catheterization, which will allow us to test how much ET-1 contributes to coronary responsiveness. The findings from this study may provide the necessary foundation to study whether endothelin receptor antagonists are able to effectively reduce the rate of accelerated CAV.

Conditions

• Cardiac Allograft Vasculopathy

Interventions

Type	Name	Description
DRUG	Macitentan	Macitentan is a nonselective endothelin-receptor antagonist (ERA) that is approved for use in pulmonary arterial hypertension (PAH); the use of Macitentan in post-heart transplant patients is considered investigational.

Timeline

• Start date: 2022-05-19
• Primary completion: 2023-02-14
• Completion: 2023-02-14
• First posted: 2022-05-13
• Last updated: 2024-03-12
• Results posted: 2024-03-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study